Takeda receives FDA approval for NINLARO (ixazomib) capsules to treat patients with multiple myeloma

Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the U.S. Food and Drug Administration (FDA) has approved NINLARO® (ixazomib) capsules, the first and only oral proteasome inhibitor, indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. NINLARO is a once-weekly pill.

Takeda submitted a New Drug Application for NINLARO to the FDA in July 2015, and in September NINLARO was granted Priority Review status with a PDUFA date of March 10, 2016, reflecting the profound and continuing unmet need for new treatments for multiple myeloma, a devastating, relapsing and incurable rare cancer.

“With the approval of NINLARO, we can now offer patients a once-weekly oral proteasome inhibitor as part of a highly active triplet therapy,” said Paul Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center Institute Physician at Dana-Farber Cancer Institute, and investigator for TOURMALINE-MM1, the pivotal Phase 3 trial on which today’s approval is based. “We, as investigators of the TOURMALINE-MM1 trial, felt it was vital to conduct a comprehensive ‘real world’ evaluation of this combination that included some of the most common patient types in the relapsed/refractory multiple myeloma setting, such as older patients, patients with moderate renal impairment, light chain disease, and high risk cytogenetics. Further, we treated patients until disease progression to determine the sustainability of NINLARO in treating their relapsed/refractory disease. The TOURMALINE-MM1 data demonstrate convincingly that oral NINLARO-based triplet treatment is effective at extending progression-free survival, over and above the clinical benefit seen with lenalidomide and dexamethasone, with a tolerable safety profile.”

Takeda receives FDA approval for NINLARO (ixazomib) capsules to treat patients with multiple myeloma

New drug combination may reduce need for complex regimens to treat hepatitis C

In continuation of my update on sofosbuvir

  

The prognosis for people with hepatitis C has improved dramatically in the last few years, thanks to the introduction of direct-acting anti-viral medications, including Harvoni (the brand name for a combination of ledipasvir and sofosbuvir) and Viekira Pack (a mix of ombitasvir, paritaprevir, ritonavir and dasabuvir). These drugs — which block the hepatitis C virus from multiplying — boast cure rates of better than 90 percent. In addition, they are well-tolerated in most patients, causing only minor side effects.

Despite these major advances, the quest for better hepatitis C medications is not yet over. Drug makers continue to test new drugs to overcome limitations in treating this virus, which can cause liver cirrhosis (or scarring) and failure. About 2.7 million people in the U.S. are infected with the virus, with nearly 30,000 cases occurring in 2013 alone, according to the Centers for Disease Control and Prevention.

"The current medicines are very effective, but physicians sometimes have to tailor the regimen or the length of treatment based on patient characteristics, such as whether the patient has liver cirrhosis or has failed prior therapy," says Nancy S. Reau, MD, chief of the Section of Hepatology at Rush University Medical Center.

Another treatment factor is the type of hepatitis C a patient has. The virus has six different strains, called genotypes.

Now a simplified way of treating all hepatitis C patients may be approaching. Reau participated in a phase III clinical trial of a combination of Solvadi (sofosbuvir) with the investigational drug velpatasvir on patients with genotypes two and three. As described in an article published online on Nov. 17 in the New England Journal of Medicine, the study found that 12 weeks of sofosbuvir-velpatasvir produced higher cure rates in patients with these two genotypes — including those who had cirrhosis or had failed older treatments — than a similar therapy (sofosbuvir-ribavirin)

New drug combination may reduce need for complex regimens to treat hepatitis C

Sildenafil drug improves insulin sensitivity in people at risk for diabetes

Sildenafil inhibits an enzyme called phosphodiesterase 5 (PDE5), resulting in relaxation of smooth muscle, vasodilation and increased blood flow. Sildenafil is used to treat erectile dysfunction and pulmonary arterial hypertension.

Animal studies suggest that sildenafil also can improve insulin sensitivity, the uptake of glucose from the bloodstream by muscle. This action can lower the level of circulating glucose, and potentially reduce the risk of diabetes.

In the current study, overweight individuals with prediabetes were randomly assigned to receive sildenafil or placebo (inactive drug) for three months. Of the 42 subjects who completed the study, those treated with sildenafil were significantly more sensitive to insulin, the researchers reported in today's Journal of Clinical Endocrinology and Metabolism.

Sildenafil drug improves insulin sensitivity in people at risk for diabetes

Identifying new mechanism for aspirin in cancer prevention

In a study published in the journal of Cancer Epidemiology, Biomarkers, and Prevention, Ulrich and her collaborators used a new technique, metabolite profiling, to identify a biochemical pathway previously unknown to be regulated by aspirin. Specifically, the researchers found that aspirin substantially decreases the level of a chemical called 2-hydroxyglutarate in the blood of healthy volunteers and in two colorectal cancer cell lines. This chemical, 2-hydroxyglutarate, is considered a driver of cancer development (known as an oncometabolite) because elevated levels have been found in certain cancers of the blood and brain and several groups are currently studying it as a molecule that promotes tumor formation.

Ulrich says the study adds to the overall evidence that aspirin is important for cancer prevention and points to a new pathway that deserves further study in the context of aspirin. "It is really exciting that aspirin, which can work in colorectal cancer prevention, is now linked to a new pathway that has shown to be relevant for cancer formation."

The first part of the study involved looking comprehensively at the metabolic profiles from the blood of 40 individuals who had taken aspirin for 60 days. The design was rigorous, with participants each having a phase with and without aspirin. More than 360 metabolites, or small molecule chemicals such as sugars, amino acids, and vitamins, were analyzed, says Ulrich. "This study covered most of the known biochemical pathways in the body."

Ref : http://cebp.aacrjournals.org/content/early/2015/11/17/1055-9965.EPI-15-0697.abstract?sid=c6453fd8-4a41-4a96-93c4-750c662bace3

Identifying new mechanism for aspirin in cancer prevention

Consuming tree nuts may reduce risk of cardiovascular disease, new study finds

In continuation of my update on the usefulness of walnuts

A new study published in the American Journal of Clinical Nutrition found that consuming tree nuts, such as walnuts, may lower the risk of cardiovascular disease. After conducting a systematic review and meta-analysis of 61 controlled trials, one of the authors, Michael Falk, PhD, Life Sciences Research Organization, found that consuming tree nuts lowers total cholesterol, triglycerides, LDL cholesterol, and ApoB, the primary protein found in LDL cholesterol. These are key factors that are used to evaluate a person's risk of cardiovascular disease. Walnuts were investigated in 21 of the 61 trials, more than any other nut reviewed in this study.

"Our study results further support the growing body of research that tree nuts, such as walnuts, can reduce the risk of cardiovascular diseases," said Dr. Falk. "Tree nuts contain important nutrients such as unsaturated fats, protein, vitamins and minerals. Walnuts are the only nut that provide a significant amount (2.5 grams per one ounce serving) of alpha-linolenic acid (ALA), the plant-based form of omega-3s."

A new study published in the American Journal of Clinical Nutrition found that consuming tree nuts, such as walnuts, may lower the risk of cardiovascular disease. After conducting a systematic review and meta-analysis of 61 controlled trials, one of the authors, Michael Falk, PhD, Life Sciences Research Organization, found that consuming tree nuts lowers total cholesterol, triglycerides, LDL cholesterol, and ApoB, the primary protein found in LDL cholesterol. These are key factors that are used to evaluate a person's risk of cardiovascular disease. Walnuts were investigated in 21 of the 61 trials, more than any other nut reviewed in this study.

"Our study results further support the growing body of research that tree nuts, such as walnuts, can reduce the risk of cardiovascular diseases," said Dr. Falk. "Tree nuts contain important nutrients such as unsaturated fats, protein, vitamins and minerals. Walnuts are the only nut that provide a significant amount (2.5 grams per one ounce serving) of alpha-linolenic acid (ALA), the plant-based form of omega-3s."

Consuming tree nuts may reduce risk of cardiovascular disease, new study finds

Lilly, Merck expand oncology clinical trial collaboration

Eli Lilly and Company (NYSE: LLY) and Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the extension of an existing collaboration to evaluate the safety and efficacy of the combination of Lilly's ALIMTA® (pemetrexed for injection) and Merck's KEYTRUDA® (pembrolizumab) in a pivotal Phase III study in first-line nonsquamous non-small cell lung cancer (NSCLC). The study will be sponsored by Merck and will be open to patients with NSCLC in the first-line setting, regardless of PD-L1 status. Financial details of the collaboration were not disclosed.

The expansion of this oncology clinical trial collaboration comes following the release of encouraging data from a Phase I study, presented earlier this year at the 16th World Congress on Lung Cancer, which evaluated pemetrexed, carboplatin and pembrolizumab in first-line nonsquamous NSCLC.

Pemetrexed is a leading therapeutic option used in combination with platinum-based therapies in this setting, making it an ideal candidate for combination studies with immunotherapy treatments. Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells – and is currently approved as a single-agent therapy for certain types of NSCLC.

Lilly, Merck expand oncology clinical trial collaboration

Anavex reports safety and efficacy data of ANAVEX 2-73 Phase 2a trial in Alzheimer’s patients

ANAVEX 2-73 (Tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride) is a σ1 agonist (IC50 = 860 nM); also displays affinity for muscarinic M1-M4 receptors (Ki values < 500 nM), but not for σ2 receptors. Exhibits neuroprotective effects, prevents tau hyperphosphorylation, and attenuates scopolamine- and (+)-MK 801-induced learning deficits in a mouse model of amyloid toxicity.

Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL). On Saturday, investigators presented positive safety and cognitive efficacy data for ANAVEX 2-73, the Company’s lead investigational oral treatment for Alzheimer’s disease targeting sigma-1 and muscarinic receptors, which are believed to reduce protein misfolding including reduction of beta amyloid, tau protein and inflammation at the international CTAD 2015 conference in Barcelona, Spain.

Initial analysis of Phase 2a data demonstrated that the study met the primary objective of safety as ANAVEX 2-73 was well tolerated and results were consistent with prior Phase 1 clinical trial data. The secondary objectives were also met, with ANAVEX 2-73 showing cognitive improvement across all doses in all exploratory cognitive measurements, including the Cogstate battery, Mini Mental State Examination (MMSE), event-related potentials (ERP) and P300 tests, which consistently demonstrated improvements from baseline in the completed PART A portion of the study in 32 mild-to-moderate Alzheimer’s patients. Even though PART A was designed as a 5 week bioavailability trial that included a built-in wash-out period of 12 days and without an optimized dosing regimen, several Cogstate tests demonstrated highly statistically significant improvements. This finding was supported by a trend towards improvement in median MMSE score, which increased by +1.5 over baseline at week 5.

Positive effects on cognition were further supported by highly statistically significant biomarker effects of treatment at week 5 on one event-related potential (ERP) measure with a p-value of p<0.0007 and improvement in the P300 signal. The ERP biomarker scores improved compared to the initial data presented at AAIC in Washington, DC in July 2015, by which time not all patients had yet completed PART A.

All patients who completed PART A volunteered to continue in the longitudinal PART B extension study.

In the interim analysis of the first 14 patients at week 12, the PART B portion of the study demonstrated a positive trend towards improvement over 12 weeks of ANAVEX 2-73 treatment on the secondary functional outcome measure, the Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory (ADCS-ADL) by +3.21 points.

Anavex reports safety and efficacy data of ANAVEX 2-73 Phase 2a trial in Alzheimer’s patients

Cotellic (cobimetinib) approved to be used in combination with vemurafenib for melanoma treatment

The U.S. Food and Drug Administration today approved Cotellic (cobimetinib) to be used in combination with vemurafenib to treat advanced melanoma that has spread to other parts of the body or can't be removed by surgery, and that has a certain type of abnormal gene (BRAF V600E or V600K mutation).

Melanoma is the most aggressive and dangerous form of skin cancer in the United States. It forms in the skin cells that develop the skin's pigment and if not diagnosed early, the cancer is likely to spread to other parts of the body. The National Cancer Institute estimates that 73,870 Americans will be diagnosed with melanoma and 9,940 will die from the disease this year.

"As we continue to advance our knowledge of tumor biology, we have learned that cancer cells have a remarkable ability to adapt and become resistant to targeted therapies. Combining two or more treatments addressing different cancer-causing targets may help to address this challenge," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Today's approval provides a new targeted treatment that, when added to vemurafenib, demonstrates greater benefit than vemurafenib alone in patients with BRAF mutation-positive melanoma."

Cotellic works by blocking the activity of an enzyme known as MEK, which is part of a larger signaling pathway. Abnormal activity of signaling pathways can lead to cancer. Cotellic prevents or slows cancer cell growth. Vemurafenib, marketed in the U.S. as Zelboraf, is a BRAF inhibitor that affects a different part of the same pathway and was approved in 2011 to treat patients with melanoma that has spread to other parts of the body or cannot be removed by surgery, whose tumors express a gene mutation called BRAF V600E, as detected by an FDA approved test. Health care providers should confirm the presence of BRAF V600 E or V600K mutation in their patients' tumor specimens using one of the available FDA approved tests prior to starting treatment with Cotellic in combination with vemurafenib.

Cotellic (cobimetinib) approved to be used in combination with vemurafenib for melanoma treatment

Diabetes drug liraglutide ineffective in patients with advanced heart failure

In continuation of my update on liraglutide

In an attempt to correct defects in the energy generation that contributes to poor pump function among heart failure patients, researchers examined whether the diabetes drug liraglutide, could improve the condition of patients with advanced heart failure. Despite improvements in blood sugar control, the therapy did not improve the clinical stability or pumping action of the heart in patients with advanced heart failure. Kenneth B. Margulies, MD, a professor of Medicine and research director for Heart Failure and Transplantation in the Perelman School of Medicine at the University of Pennsylvania, presented data from the Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT) study at the American Heart Association Scientific Sessions 2015.

Heart failure, a chronic condition in which the heart does not pump enough blood through the body, affects more than 5 million Americans.

"Abnormalities in the way the heart generates energy from fats and glucose, including resistance to the normal actions of insulin, have been shown to contribute to a patient's risk of heart failure. But no current heart failure treatments target these metabolic derangements," said Margulies, the principle investigator of the study. "Because liraglutide counters insulin resistance, and earlier pilot studies suggest that severely weakened hearts have the greatest metabolic defects and potential benefit, it seemed most appropriate test the efficacy of liraglutide in a group of patients with advanced heart failure. Unfortunately, the results were not what we had anticipated."

Diabetes drug liraglutide ineffective in patients with advanced heart failure

Drug compounds target multiple pathways associated with myotonic dystrophy type 1

Efforts to treat myotonic dystrophy type 1, the most common form of muscular dystrophy, are in their infancy. In a new study, researchers report they have added new capabilities to an experimental drug agent that previously defeated only one of DM1's many modes of action. Their retooled compounds interrupt the disease's pathology in three ways.

"We've rationally designed something to target multiple pathways, which is contrary to the traditional thinking in medicinal chemistry, where you have one target, one drug," said University of Illinois chemistry professor Steven Zimmerman, who led the research with graduate students Lien Nguyen and Long Luu. "People are slowly discovering that drugs that hit multiple targets are actually better."

The team reports its findings in the Journal of the American Chemical Society.

DM1 (but not Duchennes muscular dystrophy) results from a genetic error that causes expansion of a region of a particular gene, called DMPK. This gene includes a repeated, three-letter sequence of nucleotides, the gene's chemical building blocks. Normal cells contain as many as 35 of these repeats, but sometimes mutation pushes the number of repeats beyond 50, which can lead to symptoms of the disease. Mutant DMPK genes often continue to expand, amplifying the health problems that can result. In some people, the gene includes as many as 10,000 repeats.

Drug compounds target multiple pathways associated with myotonic dystrophy type 1

Sorafenib increases progression-free survival and disease control rate in NSCLC patients

In continuation of my update on Sorafenib

Sorafenib, a tyrosine kinase inhibitor (TKI) targeting the receptors for vascular endothelial growth factor, platelet derived growth factor, and mast/stem cell growth factor, modestly increases progression-free survival (PFS), time to progression, and disease control rate in non-small cell lung cancer (NSCLC) patients who have relapsed or failed two or three previous treatment regimens.

Lung cancer kills more people than breast, prostate, colorectal cancer combined. There are a number of treatment options now available for advanced NSCLC, the most common type of lung cancer, but almost all patients either fail or relapse after a period of clinical benefit. Patients that have relapsed or failed to respond to greater than two previous conventional chemotherapeutic treatments have very limited choices for further therapy.

A team of international investigators from 33 countries in Europe, North and South America, and Asia-Pacific conducted a relatively large phase III, randomized, double-blind, placebo-controlled trial comparing sorafenib plus best supportive care to best supportive care. This MISSION (Monotherapy admInistration of Sorafenib in patientS wIth nOn-small cell luNg cancer) trial was conducted to evaluate the efficacy and safety of sorafenib in the third or fourth-line setting with overall survival (OS) as the primary outcome measure, with PFS and other measures as a secondary endpoints.

The results published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer, show that the median PFS was statistically increased in the sorafenib (N=350) vs placebo groups (N=353) (2.8 versus 1.4 months; hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.51-0.72, p<0.0001), however the median OS was not different (8.2 versus 8.3 months; HR 0.99; 95% confidence interval [CI] 0.84-1.17, p=0.47). Time to progression was significantly greater (2.9 versus 1.4 months; HR 0.54; 95% CI 0.45-0.65, p<0.0001) with sorafenib than with placebo as was disease control rate (47.1% versus 24.7%, p=0.00086). Retrospective subgroup analyses showed that epidermal growth factor receptor (EGFR) mutation positive patients receiving sorafenib (N=44) had significantly longer OS (13.9 versus 6.5 months; HR 0.48; 95% CI 0.30-0.76, p=0.002) and PFS (2.7 versus 1.4 months; HR 0.27; 95% CI 0.16-0.46, p<0.001) than those receiving placebo (N=45).

Sorafenib increases progression-free survival and disease control rate in NSCLC patients

New protein supplement lowers cholesterol, prevents osteoporosis

Scientists developed a supplement to maintain optimal health that contributes to the growth and development of children and adolescents. It also prevents osteoporosis and certain cancers such as breast and prostate.

Prosoma is a protein supplement made from soy and amaranth, which contributes to lowering cholesterol and preventing osteoporosis, is inexpensive and was created by a group of students from the Interdisciplinary Center for Health Sciences (CICS) at the National Polytechnic Institute in Mexico City

Students Andrea Felix, Eva Fuerte, Ana Ramirez and Cesar Ramos, explained that proteins are made up of chains of amino acids, and are critical to maintaining good health as they contribute to the growth of children and adolescents, also help athletes to develop muscle and optimize their performance.

This food called Prosoma was made with soy and amaranth, vegetables that help lower cholesterol, prevent osteoporosis and certain cancers such as breast and prostate cancer, as opposed to commercial products, it contains no animal protein or chemical additives.

The team of students are specializing in Nutrition at the CICS and ensure that the mixture of these vegetables, added with small pieces of cranberry, form a functional food containing omegas 3 and 6, vitamins A, C, B1, B2 , B3, B6, K, folic acid, vitamins C and E, plus calcium, magnesium, iron, zinc, iodine, copper, selenium, phosphorus, potassium, fluorine and manganese.

According to the innovative development of Prosoma, it could help in combating malnutrition suffered by children between five and 12 years in some regions. It can be consumed by people of all ages, particularly those athletes who wish to strengthen their muscles.

New protein supplement lowers cholesterol, prevents osteoporosis

Type 2 diabetes drug significantly reduces hospitalizations, death from heart failure

In continuation of my update on Empagliflozin

For the first time, research shows that a type 2 diabetes drug significantly reduces hospitalizations and death from heart failure.

The findings, from a large clinical trial known as EMPA-REG OUTCOME, were presented by Yale professor of medicine and clinical chief of endocrinology, Dr. Silvio E. Inzucchi, at the 2015 American Heart Association (AHA) Scientific Session in Orlando, Florida on Nov. 9.

Many individuals with type 2 diabetes also have heart failure, a condition in which the heart fails to pump blood effectively. Treatment for heart failure is limited and prior efforts to treat patients with type 2 diabetes drugs showed no benefit for heart failure. But a new class of type 2 diabetes drugs (SGLT2 inhibitors) that reduce blood sugar by increasing its excretion in the urine had not been studied.

In the EMPA-REG trial, patients with type 2 diabetes and risk factors for heart disease were randomized to receive once-daily doses of either the glucose-lowering drug empagliflozin (10 mg or 25 mg doses), or a placebo. The drug or placebo was given in addition to standard care.

At the end of the trial period, investigators found that patients treated with the drug experienced reductions in blood sugar and blood pressure, as well as weight loss, compared to those on placebo. They also found major significant reductions in hospitalizations for heart failure (35%); the combined result for heart failure hospitalization or dying from heart disease (34%); and the combined result for being hospitalized or dying from heart failure (39%).

Type 2 diabetes drug significantly reduces hospitalizations, death from heart failure

Drug used to treat Parkinson's and related diseases may delay or prevent macular degeneration

In continuation of my update on L-DOPA

In a major scientific breakthrough, a drug used to treat Parkinson's and related diseases may be able to delay or prevent macular degeneration, the most common form of blindness among older Americans.

The findings, published in the American Journal of Medicine, are a groundbreaking effort in the fight against age-related macular degeneration (AMD), which affects as many as 11 million Americans. AMD hinders central vision, and even when it does not lead to blindness it can severely reduce the ability to read, drive, and recognize faces.

In the study, supported in part by BrightFocus Foundation, researchers discovered a biological connection between darker pigmented eyes, which are known to be resistant to AMD, and increased levels of a chemical called L-DOPA in those eyes. Since L-DOPA is frequently prescribed for Parkinson's patients, the researchers wanted to know whether patients who received the drug L-DOPA as treatment for Parkinson's or other diseases were protected from AMD. By combing through massive databases of medical chart data, they reported that patients receiving L-DOPA were significantly less likely to get AMD, and when they did, its onset was significantly delayed.

Drug used to treat Parkinson's and related diseases may delay or prevent macular degeneration

New therapy attacks the source of asthma, treats the disease at cellular level

Imagine you suffer from severe asthma, and you've tried every treatment available, but nothing has worked. You still can't breathe. Then a new therapy comes along that attacks the source of the asthma, as opposed to the symptoms, and treats the disease at a cellular level. That's the promise of biologics, and the topic of four presentations at the 2015 ACAAI Annual Scientific Meeting in San Antonio, November 5-9.

"Biologics is definitely something that has piqued the interest of physicians, including allergists, throughout medicine," said Kevin Murphy, MD, ACAAI Fellow and presenter at the meeting. "Traditional asthma treatments don't work for some people, and their asthma is uncontrolled. Biologics is at the cutting edge of treatment because it has the potential to be personalized - to be formulated to treat those cells which are the mechanism, or pathway, that leads to allergic inflammation and makes it so hard for some people to breathe."

Omalizumab is currently the only biologic treatment for asthma that has been approved by the Food and Drug Administration (FDA) for use in the United States, but more are in the pipeline. Allergists hope that in the next few years there could be two or three more drugs approved. Omalizumab is safe for both adults, and children over the age of 12, for treatment of severe asthma.

"It's an exciting time to be an allergist," said allergist Rohit Katial, MD, ACAAI Fellow and presenter at the meeting. "For many years, our primary tools for combatting severe asthma have been either bronchodilators, known as quick-relief medicines, or long-term control medicines which are taken every day to prevent symptoms and attacks. We also use immunotherapy, allergy shots, to reduce the allergic reactions which cause asthma attacks. Biologics target the cells and pathways that cause the allergic inflammation that has been linked to asthma."

New therapy attacks the source of asthma, treats the disease at cellular level